Where cancer genomics should go next: a clinician's perspective.

Large-scale, genomic studies of specific tumors such as The Cancer Genome Atlas have provided a better understanding of the alterations of pathways involved in the development of solid tumors including glioblastoma, breast cancer, ovarian and endometrial cancers, colon cancer and lung squamous cell carcinoma. This tremendous effort of the scientific community has confirmed the view that cancer actually represents a wide variety of diseases originating from different organs. These studies showed that TP53 and PI3KCA are the two most mutated genes in all types of cancers and that 30-70% of all solid tumors harbor potentially 'actionable' mutations that can be exploited for patient stratification or treatment optimization. Translation of this huge oncogenomic data set to clinical application in personalized medicine programs is now the main challenge for the future. The gap between our basic knowledge and clinical application is still wide. Closing the gap will require translational personalized trials, which may initiate a radical change in our routine clinical practice in oncology.

ZNF797 plays an oncogenic role in gastric cancer.

Human cancer cells resemble stem cells in expression signatures leading them to share some features, most notably, self-renewal. A complex network of transcription factors and signaling molecules are required for continuation of this trait. ZNF797 (SALL4) is a zinc finger transcriptional activator crucial for maintenance of self-renewal in stem cells; however, its expression level has not yet been elucidated in gastric tumor cells. Its expression was analyzed to determine this level and probable clinicopathological consequences. SALL4 expression in fresh tumor and distant tumor-free tissues from 46 colorectal samples was compared by real-time polymerase chain reaction. Greater than a 2-fold increase in SALL4 expression was detected in 89.5% of tumors vs normal related tissues. SALL4 expression was significantly correlated with tumor cell metastasis to lymph nodes, especially in moderately differentiated tumor samples (P < 0.05). Furthermore, higher levels of SALL4 mRNA expression were significantly associated with younger patients with tumor cells in stages I and II (P < 0.05). These results indicate a relationship between SALL4 expression and tumor cell metastasis to lymph nodes and consequent progression of tumors to advanced stages III and IV. Along with the promising evidence of its role in self-renewal in various cancers, SALL4 is introduced as a potentially interesting therapeutic target to reverse a number of aberrations that promote gastric tumor development and maintenance. This result may lead to new approaches for cancer therapy.

Absolute quantification of free tumor cells in the peripheral blood of gastric cancer patients.

Gastric cancer remains the third most common cancer in the world. Metastatic disease is a major cause of death in about half of the patients; therefore, early diagnosis is crucial for successful outcome. This study applied a sensitive method for the detection of circulating tumor cells using specific tumor markers for early detection. A total of 80 blood samples from 40 patients and 40 age-matched healthy controls were collected for the study. Circulating mRNA levels of two tumor markers, tumor endothelial marker 8 (TEM-8) and carcinoembryogenic antigen (CEA) were evaluated using absolute quantitative real-time PCR assay in the Stratagene Mx-3000P real-time PCR system. GAPDH was used to normalize the data. TEM-8 and CEA were detected in patients' blood more than in controls, 22/40 vs 9/40, P=0.005, and 30/40 vs 11/40, P=0.008, respectively. The mRNA level of these markers in patients was significantly higher in comparison to normal controls (P=0.018, 0.01). This panel showed an overall sensitivity of 64% and specificity of 73%. Statistical analysis for demographic variants did not show any significant differences. Both markers were detected more frequently and in significantly higher levels in blood samples of patients compared to samples from normal individuals. Copy number of CEA and TEM-8 mRNA, as detected by real-time quantitative PCR, appears to be a promising marker to evaluate the risk of tumor spread.

Uterine transplantation: Review in human research.

Uterine transplantation is the solution to treat absolute uterine fertility. In this review, we present the historical, medical, technical, psychological and ethical perspectives in human uterine transplantation research. We reviewed the PubMed database following PRISMA guidelines and added data presented by several research teams during the first international congress on uterine transplantation.

Topographical CT-data analysis of the human orbital floor.

The aim of this study was to evaluate the topographical anatomy of the human orbital floor for the production of prefabricated implants on the basis of computer tomography data. A database of 279 CT scans of Caucasian patients without traumatic deformation of the midface was analysed. 3D-image segmentation of the midfacial skeleton was performed using a computer-assisted protocol. A virtual plane (50 x 50 mm (2)) was constructed using defined landmarks above the orbital floor. An automated procedure was used to measure the distance between the orbital floor and the constructed plane at 400 distinct points. A mathematical algorithm was used to analyse the data, and to calculate a map of the orbital floor. Statistical analysis of the data revealed that orbital floor topography could be classified as distinct clusters. There were 12 variations of orbital floor anatomy: three unique patterns of the orbital floor for the right orbit and three corresponding patterns for the left side, all of which varied between the sexes. The 12 patterns were constructed with a statistical confidence interval of 1.36+/-0.6mm.

[Primary management of endometrial carcinoma. Joint recommendations of the French society of gynecologic oncology (SFOG) and of the French college of obstetricians and gynecologists (CNGOF)]. / Prise en charge primaire des cancers de l'endomètre : recommandations SFOG-CNGOF.

OBJECTIVES: The management of endometrial carcinoma is constantly evolving. The SFOG and the CNGOF decided to jointly update the previous French recommendations (Institut national du cancer 2011) and to adapt to the French practice the 2015 recommendations elaborated at the time of joint European consensus conference with the participation of the three concerned European societies (ESGO, ESTRO, ESMO). MATERIAL AND METHODS: A strict methodology was used. A steering committee was put together. A systematic review of the literature since 2011 has been carried out. A first draft of the recommendations has been elaborated, with emphasis on high level of evidence. An external review by users representing all the concerned discipines and all kinds of practice was completed. Three hundred and four comments were sent by 54 reviewers. RESULTS: The management of endometrial carcinoma requires a precise preoperative workup. A provisional estimate of the final stage is provided. This estimation impact the level of surgical staging. Surgery should use a minimal invasive approach. The final pathology is the key of the decision concerning adjuvant therapy, which involves surveillance, radiation therapy, brachytherapy, or chemotherapy. CONCLUSION: The management algorithms allow a fast, state of the art based, answer to the clinical questions raised by the management of endometrial cancer. They must be used only in the setting of a multidisciplinary team at all stages of the management.

In vitro and in vivo killing of ocular Demodex by tea tree oil.

AIMS: To compare the in vitro killing effect of different agents on Demodex and to report the in vivo killing effect of tea tree oil (TTO) on ocular Demodex. METHODS: Survival time of Demodex was measured under the microscope. Sampling and counting of Demodex was performed by a modified method. RESULTS: Demodex folliculorum survived for more than 150 minutes in 10% povidone-iodine, 75% alcohol, 50% baby shampoo, and 4% pilocarpine. However, the survival time was significantly shortened to within 15 minutes in 100% alcohol, 100% TTO, 100% caraway oil, or 100% dill weed oil. TTO's in vitro killing effect was dose dependent. Lid scrub with 50% TTO, but not with 50% baby shampoo, can further stimulate Demodex to move out to the skin. The Demodex count did not reach zero in any of the seven patients receiving daily lid scrub with baby shampoo for 40-350 days. In contrast, the Demodex count dropped to zero in seven of nine patients receiving TTO scrub in 4 weeks without recurrence. CONCLUSIONS: Demodex is resistant to a wide range of antiseptic solutions. Weekly lid scrub with 50% TTO and daily lid scrub with tea tree shampoo is effective in eradicating ocular Demodex.

[Exploration of breast inflammation excluding pregnancy and breastfeeding: Guidelines]. / Exploration d'une inflammation du sein en dehors de la grossesse et de la période d'allaitement: recommandations.

Breast inflammation, excluding breast-feeding and pregnancy, is a rare breast pathology. We conducted a PubMed database search of all studies focusing on mastitis or breast inflammation exploration. While the most frequent aetiologies are infectious and inflammatory, inflammatory breast cancer can be diagnosed (LE2). Aetiologic diagnostic is difficult due to the absence of any clinical and imaging specific signs (LE3). The presence of mass, suspect lymph nodes or skin thickening in a woman older than 40 years old should orient toward inflammatory breast cancer (LE3). A suspect lesion must lead to perform a biopsy under sonography (grade A). In the absence of evidence for a malignant pathology after initial evaluation, we recommend starting an antibiotic treatment (grade C) with a clinical follow-up at the end of the treatment (grade B). If the symptoms persist, we recommend a new imaging (± MRI) (grade C) and a biopsy (grade C). Benign inflammatory pathologies may require a biopsy to exclude an inflammatory breast cancer and precise the diagnosis. Their specific management and treatment are presented in detail in the following chapters and may involve steroids.

[Oncofertility program at the Montpellier university hospital 2 years after]. / Programme de préservation de la fertilité féminine au CHRU de Montpellier 2ans après.

OBJECTIVE: Female fertility preservation in the context of cancer management is crucial for patient's health care. The aim of this study was to evaluate the oncofertility practice at our university hospital of Montpellier since 2011. PATIENTS AND METHODS: The evaluation of management of young patients referred to Montpellier University Hospital from September 2011 to September 2013 for oncofertility counselling before cancer treatment. RESULTS: Seventy-one patients were referred to a specialized oncofertility center. Forty-two patients (59.1%) were included in the oncofertility program. Twenty-two patients (31%) were proposed for oocyte vitrification after COS protocol, eight patients (11.3%) for ovarian tissue cryoconservation, seven patients (9.9%) for GnRH injections, three patients (4.2%) ovarian transposition and two patients (2.8%) for embryo cryopreservation. Among the 42 indications of fertility preservation, only 18 will have finally taken place. CONCLUSION: Oncofertility counselling for young patients should now be part of the cancer management. It involves multidisciplinary teams. Further information of both oncologists and patients is needed to improve this new approach in the field of cancer treatments.

Tissue-specific somatic stem-cell isolation and characterization from human endometriosis. Key roles in the initiation of endometrial proliferative disorders.

AIM: The endometrial-proliferation related diseases leads to endometrial hyperplasia, i.e., endometriosis. Endometrial progenitor and stem cells play key roles in the beginning of endometrial proliferative disorders. The purpose of this study was the isolation of stem cells in the endometriosis lesion as well as the evaluation and comparison of the stemness-related target genes in endometriosis endometrial stem cells (EESCs), normal endometrial stem cell (ESCs), endometrial lesions stem cell (ELSCs) and bone marrow mesenchymal stem cells (MSCs). METHODS: EESCs, ESCs, ELSCs and MSCs were isolated. Flowcytometry and real-time PCR were utilized to detect the cell surface marker and expression pattern of 16 stemness genes. The proliferation of all stem cells was observed by MTT assay. The differentiation potential was evaluated by alizarin red, oil red O and RT-PCR method. The karyotyping was performed on EESCs and ELSCs at passage 20. RESULTS: The unique patterns of gene expression were detected although EESCs, ESCs, ELSCs and MSCs have a background expression of stemness-related genes. Spindle-like morphology, normal karyotype, adipogenic and osteogenic potential, significantly expression of Oct4, SALL4, DPPA2, Sox2, Sox17 and also specific surface markers such as CD44, CD105, CD90, CD73 and CD146 in EESCs and ELSCs was observed. CONCLUSION: According to our data, stem cells in endometriosis endometrial and endometriosis are such a informative tools to study of pathogenesis of gynecological diseases. Furthermore, endometrial stem/progenitor cells which easily obtain from tissue may be valuable targets for early diagnosis of endometrial disorders in the future.

[Benign breast tumors: Recommendations of Collège National des Gynécologues Obstétriciens Français (CNGOF)--Short text]. / Tumeurs bénignes du sein: recommandations pour la pratique clinique du Collège national des gynécologues et obstétriciens français (CNGOF)--Texte court.

Breast sonography is required with mammogram to explore clinical breast mass (grade B), colored unipore breast nipple discharge (grade C), or mastitis (grade C). Bi-RADS system is recommended to describe and classify breast-imaging abnormalities. For breast abscess, a percutaneous biopsy is recommended in case of mass or persistent symptoms (grade C). For mastodynia, when breast imaging is normal, no MRI neither breast biopsy is recommended (grade C). Percutaneous biopsy is recommended for BI-RADS 4-5 mass (grade B). For persistent erythematous breast nipple or atypical eczema lesion, a nipple biopsy is recommended (grade C). For distortion and asymmetry, a vacuum core needle biopsy is recommended because of the risk of underestimation by simple core needle biopsy (grade C). For BI-RADS 4-5 microcalcifications without ultrasound signal, a vacuum core needle biopsy of at least 11 gauges is recommended (grade B); in the absence of microcalcifications on radiograph carrots, additional samples are recommended (grade B). For atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ, flat epithelial with atypia, radial scar, mucocele with atypia, surgical excision is commonly recommended (grade C). Expectant management is feasible after multidisciplinary concertation. For these lesions, when excision is not in sano, no new excision is recommended except for pleomorphic or with necrosis CLIS (grade C). For grade 1 phyllode tumour, in sano surgical resection is recommended; for grade 2 phyllode, 10-mm margins are recommended (grade C). For breast papillary without atypia, complete disappearance of the radiologic signal is recommended (grade C). For breast papillary with atypia, complete surgical excision is recommended (grade C).

A psychophysical analysis of acupuncture analgesia.

A psychophysical analysis of acupuncture analgesia was carried out in which low back pain patients made visual analogue scale (VAS) responses both to their chronic pain and to different levels of experimental heat pain (5 sec exposures to 43-51 degrees C) before and after electroacupuncture. VAS (sensory) responses to chronic pain, direct temperature matches to chronic pain, and VAS (sensory) responses to experimental pain were reduced in an internally consistent manner 1-2 h after treatment. The magnitude of this analgesic response was similar for dermatomes within the region of chronic pain and acupuncture needle placement (lower back) as well as for dermatomes remote from needle placement and chronic pain (forearm). Individual patients manifested either (1) a central-inhibitory pattern of analgesia wherein experimental and chronic pain in back regions and experimental pain in forearm regions were reduced, or (2) an origin-specific pattern wherein only the chronic low back pain was reduced. Patients tested several days after treatment all manifested the latter pattern of analgesia. VAS sensory and VAS affective analgesic responses to electroacupuncture treatment showed a delayed onset (1-24 h) to maximum effect and a duration of 10-14 days. Cumulative sensory and affective analgesic effects were observed at the end of 4 months of biweekly acupuncture treatments. The results of this analysis reveal the unique spatial and temporal properties of electroacupuncture analgesia and the extent to which it is mediated by at least two different mechanisms.

A psychophysical analysis of morphine analgesia.

Intravenous administration of 0.04-0.08 mg/kg morphine sulfate reduced both sensory intensity and unpleasantness visual analogue scale (VAS) responses to graded 5 sec nociceptive temperature stimuli (45-51 degrees C) in a dose-dependent manner. The lower doses of morphine (0.04 and 0.06 mg/kg) resulted in statistically reliable reductions in affective but not sensory intensity VAS responses, possibly reflecting supraspinal effects on brain regions involved in affect and motivation. However, the highest dose of morphine tested (0.08 mg/kg) reduced both sensory and affective VAS responses to graded nociceptive stimuli as well as VAS sensory responses to first and second pain evoked by brief heat pulses. Morphine also had an especially potent inhibitory effect on temporal summation of second pain that is known to occur when intense nociceptive stimuli occur at rates greater than 0.3/sec. The results support current hypotheses about neural mechanisms of narcotic analgesia and further clarify the relative effects of morphine on sensory and affective dimensions of experimental pain. The derived morphine dose-analgesic response functions also provide a reference standard for quantitatively comparing magnitudes of different CNS-mediated forms of analgesia.

Novel polymorphism in the FMR1 gene resulting in a "pseudodeletion" of FMR1 in a commonly used fragile X assay.

The fragile X syndrome is the most commonly inherited cause of mental retardation. Genetic diagnosis of this disease relies on the detection of triplet repeat expansion in the FMR1 gene on the X chromosome. Although the majority of disease in fragile X patients is due to mutations involving triplet repeat expansion, deletion of various portions of FMR1 has also been described in association with the fragile X syndrome. Here we describe a rare polymorphism in the noncoding region of FMR1 that mimics detection of a deletion in a commonly used assay for fragile X syndrome, which can result in misdiagnosis of the disease.

Use of aerosolized inhaled epoprostenol in the treatment of portopulmonary hypertension.

BACKGROUND: Portopulmonary hypertension is a known complication in the liver transplant candidate. Intravenous epoprostenol has been demonstrated to decrease pulmonary artery pressures and possibly remodel right ventricle geometry. METHODS: In this report, we document the efficacy of inhaled aerosolized epoprostenol in a patient with portopulmonary hypertension. The effect was of rapid onset and offset. RESULTS: After 10 min of delivery, mean pulmonary artery pressure decreased 26%; cardiac output increased by 22%; pulmonary vascular resistance decreased by 42%; and the transpulmonary gradient decreased by 29%. There were no untoward side effects. CONCLUSION: The inhaled route of delivery of epoprostenol is potential alternative for the acute therapy of portpulmonary hypertension.

Analysis of peak magnitude and duration of analgesia produced by local anesthetics injected into sympathetic ganglia of complex regional pain syndrome patients.

OBJECTIVE: Pain-relieving effects of lidocaine/bupivicaine local anesthetic (LA) and saline (S) block of sympathetic ganglia (stellate block, 4 patients; lumbar sympathetic block, 3 patients) were compared in 7 complex regional pain syndrome (CRPS) patients on a double-blind crossover basis to evaluate the diagnostic and therapeutic value of local anesthetic sympathetic blocks. DESIGN: Patients rated their pain on a visual analog scale before and after blocks and were tested for mechanical allodynia one-half hour after blocks. Thereafter, they rated their pain intensity in diaries four times a day for 7 days. Each patient received two blocks, S and LA, and served as his own control. RESULTS: Both S and LA injections of sympathetic ganglia produced large reductions in pain intensity in 6 of 7 patients 30 minutes after block. These large reductions were accompanied by the reversal of mechanical allodynia in both S and LA. The mean difference between initial peak reduction in pain intensity produced by saline (68.7%) and active local anesthetic (74.4%) did not approach statistical significance. In striking contrast, the mean duration of pain relief was reliably longer in the case of LA (3 days, 18 hours) as compared with S ( 19.9 hours), a difference that occurred in all 7 patients. In a larger sample of 41 CRPS patients, signs of sympathetic efferent blockade, including Homer' s syndrome or skin surface temperature change, were not predictive of initial peak magnitude of pain relief from sympathetic blockade but were predictive of duration of pain reduction. CONCLUSION: The combination of these results provides evidence that duration of pain relief is affected by injection of local anesthetics into sympathetic ganglia. These results indicate that both magnitude and duration of pain reduction should be closely monitored to provide optimal efficacy in procedures that use local anesthetics to treat CRPS.

Predictive value of two-dimensional and three-dimensional multiplanar ultrasound evaluation of the cervix in preterm labor.

OBJECTIVE: To compare the predictive value of conventional two-dimensional ultrasound measurement of cervical length and three-dimensional multiplanar volume assessment of the cervix for delivery at < 37 weeks of gestation among patients with preterm labor. MATERIALS AND METHODS: This preliminary prospective study was conducted in 28 patients hospitalized for preterm labor between 24(+0) and 33(+6) weeks of gestation, defined by regular and painful uterine contractions (at least two per 10 min), intact membranes and a cervical length of < or = 26 mm measured by two-dimensional transvaginal ultrasonography at admission with a Voluson 530 (Kretz, France) machine using a 7.5-MHz transvaginal transducer. The cervical volume was then assessed by the three-dimensional triplan technique. It was automatically calculated after drawing of the cervix outlines in mid-sagittal and median axial plane images. As the border between the cervix and the lower uterine segment is virtual, it was defined by a perpendicular line to the line joining the external os and the internal os. The result of the latter measurement was not disclosed to the obstetric team. The primary outcome was the rate of deliveries at < 37 weeks. We constructed a receiver operator characteristic (ROC) curve to determine the optimal cut-off point of the cervical volume, to predict preterm delivery. RESULTS: Sixteen (57%) patients delivered at < 37 weeks. Mean (+/- SD) gestational ages at admission and delivery were 28.2 (+/- 3.2) weeks and 35.9 (+/- 4.1) weeks, respectively. Mean cervical length and volume at admission were 20.1 (+/- 9.9) mm and 23.1 (+/- 14.6) mm3, respectively. The ROC curve showed that the optimal cut-off point was 20 mm3. The predictive values of cervical length and of cervical volume on delivery at < 37 weeks were: sensitivity, 87.5% (14/16) and 75% (12/16); specificity, 50% (6/12) and 75% (9/12); positive predictive value, 70% (14/20) and 80% (12/15); negative predictive value, 75% (6/8) and 69.2% (9/13), respectively. CONCLUSIONS: The three-dimensional multiplanar volume assessment of the cervix probably increases the positive predictive value of cervical ultrasonography in predicting preterm delivery. Screening high-risk women could be achieved by conventional two-dimensional transvaginal ultrasound and the diagnosis of true preterm labor may be improved by three-dimensional multiplanar transvaginal ultrasound assessment of the cervix.

[Embolization of uterine arteries for uterine fibroids: state-of-the-art]. / L'embolisation des artères utérines dans le traitement des myomes utérins: état des lieux.

Embolization of uterine arteries for fibroids is a modern minimally invasive method for treatment of uterine fibroids. Results from published data show a substantial short-term uterine reduction, an improvement in menorrhagias, and a reduction in fibroid related pain. Hospital stay and recovery are shortened compared with hysterectomy. One randomised comparative trial EAU vs hysterectomy has showed a reduction in hospital stay length and in the rate of major complications, but an increased rate of minor complications. Pregnancies and uneventful deliveries have been reported after uterine arteries embolization. Rare but severe complications have been described. Embolization of uterine arteries can be considered as a safe alternative to hysterectomy or myomectomy in selected cases. It cannot be a routine method for treating fibroids with women of childbearing age.

[Prolapse in the young woman: study of risk factors]. / Prolapsus de la femme jeune: étude des facteurs de risque.

OBJECTIVE: To determine the risk factors for genital prolapse in a group of 37 young women less than 45 years old. PATIENTS AND METHODS: We studied 37 young women who had been operated for genital prolapse, whereas the control group consisted of women operated for benign gynaecologic disorders. RESULTS: In the study group the number of pregnancies and deliveries, the babies' weight, the positive family history of prolapse were heavier than in the control group. The women with prolapse had more often chronic pulmonary diseases, asthma, as well as operations for abdominal hernias. The mode of delivery, be it a cesarean section or the use of forceps, and the active second stage of labor had no effect whatever on the occurring of genital prolapse in young women. CONCLUSION: Our data support the suggestion that multiparity, babies' weight and congenital factors are responsible for a higher rate of genital prolapse in young women.

[Uterine morcellation during vaginal hysterectomy: apropos of a series of 216 prospective cases]. / Etude du morcellement utérin au cours de l'hystérectomie vaginale: à propos d'une série prospective de 216 cas.

OBJECTIVE: The purpose of this study was to compare the surgical outcomes of women undergoing vaginal hysterectomy with and without morcelation. PATIENTS AND METHOD: Between December 1999 and December 2000, 216 women underwent vaginal hysterectomy without laparoscopic assistance at the Department of Gynecology of Hôtel-Dieu hospital in Paris. The patients were divided into two groups: 114 of them underwent vaginal hysterectomies with morcelation whereas 102 underwent vaginal hysterectomies without morcelation. The two groups were compared as to demographic data, total complications, operative time, hospital stay length and peri-operative hemoglobin concentration change. RESULTS: Although women undergoing morcelation were significantly younger (mean 49 versus 52, p = 0.01) and less parous (mean 1.9 versus 2.3, p = 0.03), there were no significant differences in other surgical or anesthetic risks factors, including weight, BMI, nulliparity and preexisting surgical diseases. Mean uterine weight was significantly greater in those undergoing morcelation (331 versus 110 g, p < 0.001); operative time was increased in the group which had undergone morcelation (331 versus 110 g, p < 0.001). There were no significant differences between the two groups with respect to peri-operative hemoglobin concentration change or hospital stay length. Finally, the rate of surgical complication was similar in the two groups (17.5 versus 21.5%). CONCLUSION: Although vaginal hysterectomy requires an increase in operative time, morcelation at the time of vaginal hysterectomy is safe and facilitates the vaginal removal of enlarged uteri without increasing peri-operative morbidity.